Fingolimod therapy is not effective in a mouse model of spontaneous autoimmune peripheral polyneuropathy

Sci Rep. 2018 Apr 4;8(1):5648. doi: 10.1038/s41598-018-23949-4.

Abstract

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an autoimmune disorder, which causes progressive sensory and motor deficits and often results in severe disability. Knockout of the co-stimulatory protein CD86 in mice of the non-obese diabetic background (NoD.129S4-Cd86 tm1Shr /JbsJ) results in the development of a spontaneous autoimmune peripheral polyneuropathy (SAPP). We used this previously described transgenic model to study the effects of the sphingosine-1-phosphate receptor agonist fingolimod on SAPP symptoms, functional and electrophysiological characteristics. Compared to two control strains, knockout of CD86 in NOD mice (CD86-/- NOD) resulted in progressive paralysis with distinct locomotor deficits due to a severe sensory-motor axonal-demyelinating polyneuropathy as assessed by electrophysiological measurements. We started fingolimod treatment when CD86-/- NOD mice showed signs of unilateral hind limb weakness and continued at a dose of 1 mg/kg/day for eight weeks. We did not observe any beneficial effects of fingolimod regarding disease progression. In addition, fingolimod did not influence the functional outcome of CD86-/- NOD mice compared to vehicle treatment nor any of the electrophysiological characteristics. In summary, we show that fingolimod treatment has no beneficial effects in autoimmune polyneuropathy, which is in line with recent clinical data obtained in CIDP patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / pathology
  • B7-2 Antigen / physiology*
  • Disease Models, Animal*
  • Female
  • Fingolimod Hydrochloride / pharmacology*
  • Immunosuppressive Agents / pharmacology*
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Peripheral Nervous System Diseases / drug therapy*
  • Peripheral Nervous System Diseases / pathology
  • Polyneuropathies / drug therapy*
  • Polyneuropathies / pathology
  • Treatment Outcome

Substances

  • B7-2 Antigen
  • Cd86 protein, mouse
  • Immunosuppressive Agents
  • Fingolimod Hydrochloride